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Immunology-Nicole > Immune Assignment #2 > Flashcards

Immune Assignment #2 Flashcards

1
Q

Describe the phagocytic ability of monocytes

A

have limited phagocytic activity

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2
Q

Describe the phagocytic ability of macrophages

A

are specialized phagocytes

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3
Q

Describe the phagocytic ability of neutrophils

A

have exceptional phagocytic ability

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4
Q

Describe differentiation of monocytes in bone marrow

A

CCL/MCP-1 (Monocyte chemotatic factor-1) attracts monocytes into circulation and into tissues.
Activated monocytes secrete cytokines (GM-CSF, G-CSF, and M-CSF

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5
Q

Monocytes secrete GM-CSF, G-CSF, and M-CSF. describe the role of each

A

GM-CSF: Role in differentiation of a myeloid progenitor to a GM progenitor.
G-CSF: Role in differentiation of a myeloid progenitor to a granulocyte in hematopoiesis
M-CSF: Role in differentiation of a myeloid progenitor to a monocyte in hematopoiesis.

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6
Q

Explain the role of CCL2/MCP-1.

A

Mobilization and chemotaxis to site of inflammation

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7
Q

Effect of GM-CSF on dendritic cells

A

Enhances dendritic cell maturation, proliferation and migration

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8
Q

Describe macrophages with respect to: differentiation from monocytes

A

Monocytes enter circulation

Monocytes leave circulation and enter tissues and become macrophages

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9
Q

Describe macrophages with respect to: role of MCP-1/CCL-2 in absence and during infection

A

Chemokine CCL-2/MCP-1 enhances recruitment of monocytes into circulation and migration into tissues where they differentiate into macrophages (during infection)

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10
Q

list the names of macrophages as a function of tissue

A 
CNS ---> Microglial cells 
Liver ---> Kupffer cells 
Synovium ----> Synoviocytes 
Lung ---> Alveolar macrophages 
Lymph and spleen ---> macrophages
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11
Q

List the two main roles of macrophages

A
  1. Phagocytosis (direct regonition, indirect recognition and leads to cytokine and chemokine secretion)
  2. Antigen presenting cells for CD4 + T cells
    (remember not as effective as dendritic cells)
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12
Q

Recognition of antigens/pathogens is direct or indirect. Explain the term direct recognition

A

very simply —> immediate recognition of a pathogen by a phagocyte

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13
Q

Explain the role of pattern recognition receptors on phagocytes

A

PRRs (pattern recognition receptors) interact directly with pathogens via PAMPs (pattern associated molecular patterns)
PRRs distinguish pathogens from self. PRRs exist as membrane bound receptors, cytosolic receptors, or secreted receptors. These receptors trigger cascades of biochemical events that lead to secretion of inflammatory cytokines, and other cellular responses associated with innate immune responses.

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14
Q

Name one family of proteins that are classed as PRRs

A

a group of membrane bound receptors that exist both as cytosolic vesicles and external cell membranes are the toll like receptors (TLRs)

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15
Q

Explain the role of pathogen associated molecular patterns on pathogens (PAMPs)

A

Ligands, or molecules expressing the molecular patterns on pathogens.
PRRs interact directly with pathogens via PAMPs.

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16
Q

Describe the steps in phagocytosis and formation of phagosome.

A

Phagocytosis is a process of internalization and degradation. Recognition and binding of the pathogen is followed by its ingestion as a portion of a plasma membrane extends outward and surrounds the microbe.
This extension outward and surround of the microbe forms a phagocytic vacuole termed phagosome.

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17
Q

Describe the steps in formation of a phagolysosome

A

Lysosomes, present in the cytosol, fuse with the phagosome to form a fusion product, the phagolysosome, into which lysosomal granules are discharged.

18
Q

List the armamentarium generated from NAPDH oxidase

A 
Superoxide (forms hydrogen peroxide)
Hydrogen Peroxide 
Hydroxyl Radical 
Hydroxyl Ion 
Hypochlorite (source myeloperoxidase); a potent anti-microbial agent
19
Q

List the armamentarium generated from lysosomal fusion

A

Lactoferrin
lysozyme
defensins
Myeloperoxidase (produces hypochlorite)

20
Q

List the armamentarium generated from iNOS

A

inducible nitric oxide synthase

product: NO and other RNIs

21
Q

Describe the effect of IFNgamma on macrophage activation and the source of these cytokines

A
  1. Role in NAPDH oxidase and iNOS activity (enhances NADPH oxidase activity and activates iNOS)
  2. Source —> secreted by NK cells and secreted by Th1 cells (main producer)
22
Q

Describe the effect of TNF on macrophage activation and the source of these cytokines

A
  1. Role in NADPH oxidase and iNOS activity (enhances NADPH oxidase activity and role in iNOS activation)
  2. Source —> secreted by macrophages and Th1 cells (main producer)
23
Q

Describe the effect of IL-4, IL-10 and TGFB on macrophage activation and the source of these cytokines

A
  1. Role in iNOS downregulation (down regulate iNOS; TGFB is most effective)
  2. Source —> TGFB is secreted by Th2 cells and macrophages. IL-10 and IL-4 are secreted by Th2 cells
24
Q

List the chemokines secreted by activated macrophages

A

Activated macrophages secrete chemokines IL-8/CXCL8 and MCP-1/CCL2 (target cells —>neutrophils and monocytes, respectively) (role –> chemotactic)

25
Q

List the cytokines secreted by activated macrophages

A

IL-1 + TNF —-> target cells are vascular endothelial cells and the role induces vascular endothelial to secrete CXCL-8 (IL-8) and MCP-1 (CCL2).
TGFB —> target cells are iNOS, Th17 cells and a/i Treg cells and its role is to down regulate iNOS phagocytes
IL-6 —> target cells are hepatocytes and Thp cells and its role is to bind to hepatocytes to secrete C-reactive protein (CRP)
IL-12 —> Target is NK cells but role is to activate NK cells to secrete IFNgamma
IL-15/IL-18 —> target cells NK cells and role is to enhance IFNgamma secretion induced by IL12
IL-23 —> target cells Th17 cells and its role is stabilization of Th17 cells during differentiation of Thp cells to Th17 cells.

26
Q

Describe the inflammasome

A

The NALP3 inflammasome is a large multi-protein complex that plays a critical role in the host defense by mediating the conversion of the zymogen, procaspase-1 to caspase-1. Caspase-1 converts pro-IL-1 and and pro-IL-18 to biologically active forms (IL-1 and IL-18) which are secrete from the macrophage.

27
Q

Describe the signal 1 and signal 2 in the inflammasome

A

The release of IL-1 and IL-18 is a two signal process: (i) signal 1 is activation of NFkB following PAMP binding to PRR, which leads to transcription of pro-IL-1 and pro-IL-18. (ii) signal 2 from DAMP causes the conversion of pro-caspase 1 to caspase-1. Caspase-1 then cleaves the biologically active precursors to their active forms IL-1 and IL-18, which are then secreted from the cells

28
Q

List 5 examples of DAMPS

A

Molescules that trigger signal 2 are referred to as danger associated molecular patterns (DAMPS). (i) numerous molecule released during trauma or cell death. (ii) reactive oxygen species, (iii) ATP, (iv) cholesterol crystals, (v) free fatty acids

29
Q

Describe the role of IL-1 and TNF on vascular endothelium in an inflammatory response

A

Secreted by macrophages –> synergistic effect
ILF and TNF —> (i) secrete CXCL8 (IL-8) and MCP-1 (CCL2); (ii) express E selectin, VCAM-1 and ICAM-1; (iii) upregulate expression of ICAM-2.

VCAM-1 on vascular endothelium interaction with VLA-4 on monocytes, lymphocytes, and eosinophils. ICAM-1 and ICAM-2 on vascular endothelium interact with LFA-1 on neutrophils, monocytes, lymphocytes and eosinophils

30
Q

List the three opsonins that may be deposited on a pathogen. list their receptors as well

A
  1. FCgammaR —–> IgG
  2. CR-1 (complement receptor) —> C3b
  3. CRP binding site —> CRP
    (note receptors are on the phagocyte)
31
Q

Explain how the opsonins were generated

A

Opsonins are generated when components other than phagocytes are activated in response to the pathogen

32
Q

Explain why opsonin-mediated recognition is called indirect recognition

A

Follows antibody production!!
Phagocytes recognize pathogens indirectly using cell surface receptors that recognize molecules that have bound to, or been deposited, on the pathogen cell surface

33
Q

Explain the consequence of CD200R interaction with CD200

A

Phagocyte responses are regulated by multiple factors as well as by cell surface receptors, including inhibitory signals resulting from ligation CD200R by the widely distributed membrane protein, CD200.

34
Q

Is CD200R on the cell being sent a negative signal or the cell sending the negative signal?

A

CD200R is on the cell being sent the negative signal

35
Q

Explain why macrophages are not as effective as antigen presenting cells as dendritic cells

A

Secondary immune responses generally occur at the site of infection, while, primary immune responses occur in secondary lymphoid tissues and not at the site of infection. Dendritic cells can actually capture antigen in the periphery and transport it to the appropriate lymphoid tissue

36
Q

For antigen presentation by macrophages

A

Antigen presenting cells (present) antigen fragments to CD4 T cells.

37
Q

Describe neutrophils

A
  1. Do not function as antigen presenting cells
  2. Do not secrete cytokines or chemokines
  3. Recognition is the same as that described for macrophages
  4. Armamentarium products and functions are that as described for macrophages.
38
Q

Neutrophils- differentiation

A

Neutrophils mature from precursor cells in the bone marrow under influence of G-CSF

39
Q

Neutrophils- percent circulating leukocytes

A

60% of circulating leukocytes in peripheral blood

40
Q

Neutrophils- half life in circulation

A

Once neutrophils are released into circulation they have a half life of some 8 hours

41
Q

Neutrophils- chemotatic factors that attract neutrophils to site of inflammation

A

A number of chemotactic factors (IL-8/CXCL8 and C5a) generated in the early phase of an inflammatory response result in enhanced release of neutrophils from the bone marrow and attraction to the site of inflammation.

Immunology-Nicole (20 decks)

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